R.M.J. Palmer's research while affiliated with University of Nottingham and other places

Publications (64)

Article
Full-text available
1. A cascade superfusion technique has been developed for the differential bioassay of prostacyclin and Endothelium-Derived Relaxing Factor (EDRF) released from porcine aortic endothelial cells cultured on microcarriers, packed into a column and perfused. 2. Bradykinin (Bk; 20-100 nM) released prostacyclin (9.6 ±1.5 nM per 106 cells; mean ± s.e.mea...
Article
1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP...
Article
Full-text available
Incubation of human articular chondrocytes with interleukin 1 beta results in the time-dependent expression of nitric oxide (NO) synthase. We report here the isolation of a cDNA clone which encodes a protein of 1153 amino acids with a molecular mass of 131,213 Da and a calculated isoelectric point of 7.9. CHO cells transfected with a plasmid harbor...
Article
Endothelium-denuded strips of rabbit thoracic aorta relax on exposure to light. This response is similar to endothelium-dependent relaxation as it is inhibited by hemoglobin and methylene blue, and is mediated by an increase in cyclic GMP. We now demonstrate that photorelaxation decreases on repeated exposure to light. The response can be restored...
Article
Incubation of human chondrocytes with interleukin-1 beta, tumour necrosis factor or endotoxin induced the expression of NO synthase. The synthesis of NO induced by IL-1 beta was concentration- and time- dependent, occurred after a lag period of approximately 6h and was inhibited by NG-monomethyl-L-arginine, cycloheximide, dexamethasone and hydrocor...
Article
Full-text available
Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) togeth...
Article
The effect of interleukin(IL)-8 and leukotriene B4 (LTB4) on the induction of nitric oxide (NO) synthase in rat peritoneal neutrophils (PMN) ex vivo was studied. IL-8, but not LTB4, caused concentration-dependent inhibition of the induction of a Ca(2+)-independent NO synthase ex vivo. The effect of IL-8 was not attributable to the synthesis of an i...
Article
Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determ...
Article
Full-text available
Incubation of vascular endothelial cells with S.typhosa endotoxin and interferon-gamma caused a time- and concentration-dependent reduction in the viability of the cells. The cytotoxic effect was inhibited in a concentration-dependent manner by NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, and by the glucocorticoids dexamet...
Article
The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied b...
Article
Full-text available
Nitric oxide (NO) is synthesized by a number of cells from a guanidino nitrogen atom of L-arginine by the action of either constitutive or inducible NO synthases, both of which form citrulline as a co-product. We have determined the source of the oxygen in both NO and in citrulline formed by the constitutive NO synthase from the vascular endotheliu...
Article
Hypotension in septic shock is often resistant to treatment with vasoconstrictors and appears to be mediated by production of nitric oxide (NO). Reversal of endotoxin-induced hypotension in rats was achieved by intravenous injection of 30 mg/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endogenous NO synthesis. A lower dose of 3 mg/kg L-NMM...
Article
Citrulline is formed as a co-product in the biosynthesis of nitric oxide from L-arginine by the action of either constitutive or inducible nitric oxide synthase which is present in a variety of cells. We have previously shown that the oxygen atom incorporated into both nitric oxide and citrulline derives from molecular oxygen and not water. This pa...
Article
Full-text available
In the absence of light, high concentrations of cGMP open ion channels in the plasma membranes of rod outer segments. The source of stimulation of retinal guanylate cyclase is not known. Nitric oxide is a potent stimulator of guanylate cyclase in other cell systems. The present data demonstrate that nitric oxide synthase, an enzyme responsible for...
Article
The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). In four aw...
Article
Full-text available
The mechanism of the increased sensitivity to nitrovasodilators after removal of endothelial nitric oxide (NO) was investigated in vitro and in vivo. The vasoconstrictor potency of phenylephrine and the force of contraction of rat isolated aortic rings were significantly enhanced after endothelium removal or treatment with inhibitors of endothelial...
Article
1. The synthesis of nitric oxide (NO) from L-arginine by rat peritoneal neutrophils (PMN) and the murine macrophage cell-line J774 and the inhibition of this synthesis by N-iminoethyl-L-ornithine (L-NIO), NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine (L-NNA) and its methyl ester (L-NAME) were investigated. 2. L-NIO was the most potent inhi...
Article
The relationship between vascular tone and the induction by endotoxin of a nitric oxide (NO) synthase was studied in vitro in rings of rat thoracic aorta. In rings with and without endothelium there was a time-dependent induction of NO synthase accompanied by both spontaneous and L-arginine-induced relaxation and by reduced contractility to phenyle...
Article
Nitric oxide (NO) is synthesized from l-arginine by an enzyme called the NO synthase. NO production by vascular endothelial cells accounts for the biological properties of endothelium-derived relaxing factor and maintains a vasodilator tone. Platelets also produce NO, which modulates their aggregability. In the central nervous system NO mediates th...
Article
Full-text available
Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found that these cells express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO synthase that is distinct from the constitutive enzyme. The generation of NO by this enzyme was...
Article
Full-text available
1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO...
Article
1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denu...
Article
1. The activation of the L-arginine: nitric oxide (NO) pathway during aggregation of human platelets by adenosine 5'-diphosphate (ADP), arachidonic acid, thrombin and the calcium ionophore A23187 and its inhibition by NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and N-iminoethyl-L-ornithine (L-NIO) were studied. The...
Article
1The activation of the l-arginine:nitric oxide (NO) pathway during aggregation of human platelets by adenosine 5′-diphosphate (ADP), arachidonic acid, thrombin and the calcium ionophore A23187 and its inhibition by NG-monomethyl-l-arginine (l-NMMA), NG-nitro-l-arginine methyl ester (l-NAME) and N-iminoethyl-l-ornithine (l-NIO) were studied. The inh...
Article
Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hind...
Article
Full-text available
The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax....
Article
Full-text available
Aggregation of human washed platelets with collagen is accompanied by a concentration-dependent increase in cyclic GMP but not cyclic AMP. NG-Monomethyl-L-arginine (L-MeArg), a selective inhibitor of nitric oxide (NO) synthesis from L-arginine, reduces this increase and enhances aggregation. L-Arginine, which has no effect on the basal levels of cy...
Article
Full-text available
Aggregation of human washed platelets with collagen is accompanied by a concentration-dependent increase in cyclic GMP but not cyclic AMP. NG-Monomethyl-L-arginine (L-MeArg), a selective inhibitor of nitric oxide (NO) synthesis from L-arginine, reduces this increase and enhances aggregation. L-Arginine, which has no effect on the basal levels of cy...
Article
The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-...
Article
An endothelium-derived relaxing factor (EDRF) has recently been identified as nitric oxide (NO), originating from endothelial cell metabolism of L-arginine. In vitro studies suggest that EDRF/NO stimulates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels in vascular smooth muscle cells, resulting in the vas...
Article
The formation of nitric oxide (NO) by an L-arginine:NO synthase and its stimulation of the soluble guanylate cyclase was studied in rat whole adrenal and bovine cortex and medulla cytosol. In the presence of L-arginine, the stimulation of soluble guanylate cyclase was accompanied by the formation of citrulline and NO2-, formed from NO. The NO synth...
Article
Full-text available
1. The role of nitric oxide (NO) in the regulation of the vascular tone of the coronary circulation of the Langendorff-perfused rabbit heart was investigated. 2. NG-monomethyl-L-arginine (L-NMMA; 10-100 microM), a specific inhibitor of NO formation from L-arginine (L-Arg), but not its D-enantiomer (D-NMMA; 100 microM) produced a dose-related, susta...
Article
Full-text available
A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological conce...
Article
Stimulated rat peritoneal neutrophils release a platelet inhibitory factor with the pharmacological properties of NO. This release is inhibited by NG-monomethyl-L-arginine and L-canavanine, indicating that it occurs through a mechanism similar to that in vascular endothelial cells and macrophages. As the degree of stimulation increases, the factor...
Article
Full-text available
The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arte...
Chapter
The importance of the endothelium in vessel wall homeostasis has recently become apparent. The vascular endothelium has been discovered to generate two potent vasodilators, prostacyclin (Moncada et al., 1976) and endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) in response to a number of chemical or mechanical stimuli. Prost...
Article
: The formation of nitric oxide (NO) by an L-arginine:NO synthase and its stimulation of the soluble guanylate cyclase was studied in rat whole adrenal and bovine cortex and medulla cytosol. In the presence of L-arginine, the stimulation of solu_ble guanylate cyclase was accompanied by the formation of ci)tj_rulline and NO, , formed from NO. The NO...
Article
1. Acetylcholine (ACh, 0.03-3.0 microM) induced a dose-dependent vasodilatation in the isolated Langendorff-perfused heart of the rabbit. The vasodilatation was mimicked by exogenous nitric oxide (NO, 0.045-4.5 nmol). 2. There was no detectable vascular relaxing activity in the cardiac effluent when these concentrations of ACh or NO were injected t...
Article
Full-text available
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. Thes...
Article
Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue1 and for the inhibition of platelet aggregation2 and platelet adhesion3 attributed to endothelium-derived relaxing factor4. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Ni...
Article
Nitric oxide (NO) was compared with prostacyclin as an inhibitor of the activation of human platelets during isolation, washing and storage. The use of NO throughout the procedure prevented the activation of platelets. The morphology and behaviour of NO-washed platelets was similar to that of prostacyclin-washed platelets when stored at 4 degrees C...
Article
1. The interactions between endothelium-derived nitric oxide (NO) and prostacyclin as inhibitors of platelet aggregation were examined. 2. Porcine aortic endothelial cells treated with indomethacin and stimulated with bradykinin (10-100 nM) released NO in quantities sufficient to account for the inhibition of platelet aggregation attributed to endo...
Article
The adhesion of human platelets to monolayers of bovine endothelial cells in culture was studied to determine the role of endothelium-derived nitric oxide in the regulation of platelet adhesion. The adhesion of unstimulated and thrombin-stimulated platelets, washed and labelled with indium-111, was lower in the presence than in the absence of brady...
Article
1 The pharmacological effects of endothelium-derived relaxing factor (EDRF), nitric oxide (NO) and prostacyclin on human and rabbit platelets were examined. 2 EDRF is released from porcine aortic endothelial cells, cultured on microcarriers and treated with indomethacin, in sufficient quantities to inhibit platelet aggregation induced by 9,11-dideo...
Article
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO fr...
Article
Full-text available
The mechanism of the inhibitory action of phenidone, 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C), dithiothreitol, hydroquinone, and pyrogallol on the vascular relaxation induced by endothelium-derived relaxing factor (EDRF) was investigated. EDRF was released from porcine aortic endothelial cells in culture and bioassayed on a casc...
Article
A cascade superfusion technique has been developed for the differential bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) released from porcine aortic endothelial cells cultured on microcarriers, packed into a column and perfused. Bradykinin (Bk; 20-100 nM) released prostacyclin (9.6 +/- 1.5 nM per 10(6) cells; mean +/- s.e.me...
Article
Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structu...
Chapter
The mechanism by which non-steroidal anti-inflammatory drugs (NSAID), such as aspirin and indomethacin, provide symptomatic relief for patients with inflammatory disease is generally recognised to be by inhibition of the formation of prostaglandins (PG’s) from arachidonic acid (AA). The evidence for the involvement of PG’s in inflammation is that e...
Article
The release of leukotriene B4 (LTB4) from human neutrophils and its relationship to degranulation induced by the divalent cation ionophore A23187, serum-treated zymosan (STZ), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and arachidonic acid (AA) have been studied. Greatest release of LTB4, measured by specific radioimmunoassay, occurred in respo...
Article
Arachidonic acid is released by the action of phospholipase and can be oxygenated by two known pathways. Cyclo-oxygenase is present in every tissue and is activated whenever tissues are damaged or stimulated. Cyclo-oxygenase products are powerful mediators of inflammatory erythema, oedema and hyperalgesia. The lipoxygenase product 5,12-DHETE (Leuko...
Article
A number of hydroperoxy (HPETE) and hydroxy (HETE) products of the lipoxygenase pathway of arachidonic acid metabolism are chemotactic and chemokinetic for human neutrophils. We have investigated the relative chemokinetic potency of some of these products on human, rat and rabbit neutrophils. The most potent lipoxygenase product studied was 5,12-di...
Chapter
Mono-hydroxy acids derived from arachidonic acid (AA) via the lipoxygenase pathway have been reported to be chemokinetic and chemotatic for human leukocytes, 5-hydroxyeicosatetraenoic acid (5-HETE) being the most potent1. In the present study we have investigated the metabolism of AA in rat and rabbit peritoneal exudate cells (PEC) and in human leu...
Article
Therole ofendothelium-derived nitric oxide intheregulation ofblood pressure intheanesthetized rabbit wasstudied withNa-monomethyl-L-arginine (L-NMMA), a specific inhibitor ofits formation fromL-arginine. L-NMMA (3-100 mg-kg-'), butnotitsD-enantiomer, induced adose- dependent long-lasting (15-90 min)increase inmeansystemic arterial blood pressure. L...

Citations

... NO, as a simple gaseous small molecule, can easily diffuse through the cell membrane and plays an important role in the organisms (Calabrese et al. 2009;Li et al. 2018). NO was reported to be synthesized in mammals and involved in many physiological processes of plant, such as seed germination, growth, stomatal movement, photosynthesis, respiration, cell transportation, cell death, immune system, and stress response (Palmer et al. 1987;Takahashi and Yamasaki, 2002;Guo and Crawford, 2005;Floryszak-Wieczorek and Arasimowicz-Jelonek, 2016;Fu et al. 2016;Oliveira et al. 2016;Wang et al. 2017). Macrofungi, a multicellular organism, have many characteristics different from plants and animals. ...
... Among these, two pathways are poten- tially related to regulation of the activity of vascular smooth muscle. One is production of nitric oxide(NO), mediated by nitric oxide synthase (24), and the other is formation of agmatine by the enzyme arginine de- carboxylase. ...
... The connection between Arg and migraine is its participation as a substrate for NOS catalyzed NO production that in turn stimulates vasodilation, initiating and exacerbating episodic migraine, and may also be involved in pronociception, again exacerbating migraine. In NO-induced vasodilation, NO produced in the vascular endothelium, the surrounding smooth muscle, or nitrergic neurons activates guanylyl cyclase to convert guanosine triphosphate (GTP) to cGMP which, through subsequent activation of protein kinase G, promotes the uptake of calcium by the sarcoplasmic reticulum (SR), leading to relaxation of surrounding smooth muscle [231][232][233]. ...
... At this stage, inflammatory cells are recruited and the secretion of greater amounts of growth factors, chemokines, cytokines, and secondary metabolites to eliminate invading pathogens occurs [50][51][52]. Nitric oxide (NO) is as an example of such an inflammatory mediator, being a highly permeable molecule that quickly diffuses through membranes [53,54]. If all these mediators are produced in appropriate amounts, the inflammatory response is helpful. ...
... NO is produced by iNOS in macrophages, hepatocytes, and renal cells, under the stimulation of LPS, tumor necrosis factor-alpha (TNF-), interleukin-1 (IL-1), or interferon-gamma (IFN-) [33]. The overproduction of NO by iNOS has been implicated in the pathology of several inflammatory disorders, including septic shock, tissue damage after inflammation, and rheumatoid arthritis [34][35][36]. Therefore, inhibiting iNOS activity or downregulation of iNOS expression is one of the ways to reduce inflammation. ...
... Nitric oxide (NO) is a ubiquitous gaseous radical species [6,7] present in the immune [8], and urinary system [9] of various species and endocrine tissues [10,11] among others [12][13][14]. Many studies [15,16] have suggested various contributing factors for chronic renal failure (CRF) like protein nitration, nitric oxide (NO) inactivation, hypertension, and functional NO deficiency. ...
... These enantiomer-specific effects run parallel to those observed on endothelium-derived relaxing factor (EDRF)-mediated relaxations of vascular smooth muscle (Rees et al., 1989), and to those observed in rat anococcygeus muscle (Li & Rand, 1989; Gillespie et al., 1989) and gastric fundus (Li & Rand, 1990a). In addition, L-NAME was more potent (by a factor of 10-30) than L-NMMA in reducing NANC stimulation-induced relaxations, and is more potent (by a factor of 20) than L-NMMA as an inhibitor of NO synthesis (Schulz et al., 1990). These findings suggest that a component of the NANC-induced relaxation of guinea-pig tracheal smooth muscle is mediated by NO. ...
... Both these reactions were proposed as feedback inhibitory signaling mechanisms for preventing undesired platelet activation. In numerous papers, starting from the first indication that platelets themselves produced NO by activation of NOS [33,34], inhibition of platelet activation by NO derived from platelets was shown (rev. in refs. [35][36][37]). ...
... It suggested that RDN could rectify the metabolism disorder of the carrageenan-induced inflamed rats. The metabolic neural network was constructed between the above four biomarkers and the known inflammation-related small molecules, including histamine (Hasala et al., 2008;Sato et al., 2020), arachidonic acid (Higgs, Palmer, Eakins, & Moncada, 1981;Trostchansky, Moore-Carrasco, & Fuentes, 2019), leukotriene B4 (Wan, Tang, Stsiapanava, & Haeggstrom, 2017), PGE 2 . The results showed they were closely related (Fig. 7), indicating that the screened inflammation-related biomarkers had certain reliability. ...
... Additionally, NO modulates steroidogenesis in various endocrine tissues [120]. Rodent and bovine adrenal glands have an active NOS system, which is NADPH and calcium dependent and can be inhibited by L-arginine analogs [121]. NO inhibits cytochrome P450 cholesterol side chain-cleaving enzyme (CYP11A1, P450scc) [122], the rate-limiting catalytic step in steroidogenesis. ...